A hole in the T cell repertoire specific for a pigeon cytochrome c related peptide associated with amino acid substitutions on I-Ab molecules.

When C57BL/10(B10) mice were immunized with a pigeon cytochrome c related peptide, 50V (AEGFSYTVANKNKGIT), two helper T cell populations with different specificity were activated. A major T cell population reacted with a 50V analog, 50V54A (AEGFSYTVANKAKGIT), more potently than with the immunogen, 50V, in a heteroclitic fashion, whereas the other minor T cell population responded only to 50V. By contrast, when bm12 mice were immunized with 50V, the minor T cell population responding only to 50V could hardly be demonstrated. The apparent deletion of the minor T cell population in bm12 mice seems to be attributable to negative selection under the influence of I-Abm12 molecules, since the minor T cell population was undetectable in both I-Ab and I-Abm12 restricted T cells from (B10 x bm12)F1 mice. Thus, three mutant points on the I-A molecule in bm12 mice appear to be involved in the seemingly negative selection of the certain T cell repertoire. The present finding demonstrates that a T cell repertoire generated under the influence of a MHC product (Ab) on one parental strain is eliminated by a different MHC product (Abm12) on the other parental strain of F1 cross. The mechanism underlying the apparent negative selection is discussed.     

Clinical and manometric evaluation of anorectal function following low anterior resection with low anastomotic line using an EEA™ stapler for rectal cancer

Anorectal function was evaluated in eight patients who had low anterior resection of the rectum with a low anastomotic line, using an EEA^™ stapler, with determination of function based on periodic manometric studies and clinical symptoms. Immediately following surgery all patients suffered from frequent bowel actions and soiling. These symptoms improved with time and most patients could enjoy almost normal daily life by the sixth postoperative month. One month after surgery, anal canal resting pressure and maximum squeeze pressure were significantly reduced and rectoanal inhibitory reflex was absent; neither showed a distinct tendency to improve thereafter. Rectal sensation and reservoir capacity, which also were seriously impaired, recovered satisfactorily by the time of the six-month examination. This suggests that an improvement of clinical symptoms following this operation is dependent upon the recovery of reservoir capacity and sensation of the neorectum, and that this operative procedure is a functionally acceptable option for low rectal cancer.     

Body temperature monitoring in subjects with delayed sleep phase syndrome

To clarify the circadian aspects of delayed sleep phase syndrome (DSPS) in 4 patients with DSPS, we recorded polysomnograms and rectal temperature before and after chronotherapy. The time interval (2.7 h) between sleep onset and rectal temperature minimum before chronotherapy was shorter than the time interval after chronotherapy (5.3 h). Before chronotherapy, the period of rectal temperature rhythm was 24.7 h. After chronotherapy, the period of rectal temperature rhythm was 24.0 h. These findings lead to the conclusion that in DSPS there is a weakened mechanism of entrainment similar to that in non-24-hour sleep-wake syndrome.     

Enhanced clearance of lactic dehydrogenase-5 in severe combined immunodeficiency (SCID) mice: effect of lactic dehydrogenase virus on enzyme clearance.

The lactic dehydrogenase (LDH) level in plasma and the clearance of LDH in C.B-17 scid (severe combined immunodeficiency; SCID) mice were compared with those in C.B-17 or BALB/cCrSlc mice with or without lactic dehydrogenase virus (LDV) infection. The resting enzyme level in SCID mice showed little difference from that in C.B-17 or BALB/cCrSlc mice. The degree of increased plasma LDH level in SCID mice was lower than that in C.B-17 and BALB/cCrSlc mice after LDV infection. To assess the mechanisms of decrease in LDH elevation in SCID mice infected with LDV, virus replication was compared in SCID and BALB/cCrSlc mice. The infectivity titre of plasma in SCID mice was higher (more than 10 times) than that in BALB/cCrSlc mice. Moreover, the percentage of virus antigen positive Kupffer cells was higher in SCID mice than that in BALB/cCrSlc mice. The level of endogenous LDH release as a result of carbon tetrachloride treatment was similar in the SCID and BALB/cCrSlc mice. The clearance rate of endogenous LDH was greater in SCID mice than in BALB/cCrSlc mice with or without LDV infection. The rate of clearance of intravenously injected porcine LDH-5, but not porcine LDH-1, was enhanced in SCID mice as compared with that in BALB/cCrSlc mice. Furthermore, carbon clearance was higher in SCID mice than that in BALB/cCrSlc mice. These results suggest that the smaller increase of plasma LDH after infection might be due, at least in part, to the enhanced LDH-5 clearance function by macrophages in SCID mice.     

Gastric leiomyoblastoma: report of a case

The case of a 38-year-old man with an exogastric leiomyoblastoma is reported. CT and ultrasound examinations revealed a large mass in the left hypochondrium that had both solid and cystic components. These findings mimicked those of cystadenoma of the pancreas. Because of intraperitoneal hemorrhage in the preoperative course, emergency laparotomy was performed. A large tumor was found to arise from the greater curvature of the stomach. The diagnosis was confirmed histologically.     

Retention fluids of chronic sinusitis induce neutrophil adherence to microvascular endothelial cells.

The adherence of circulating leukocytes to the vascular endothelium is a critical step in the emigration of leukocytes through blood vessel walls to inflammatory lesions. The influence of nasal secretions on the adherence of neutrophils to the vascular endothelium was investigated using monolayers of human mucosal microvascular endothelial cells derived from the inferior turbinate. Preincubation of vascular endothelial cells with retention fluids from the maxillary sinus of the patients with chronic sinusitis showed increased neutrophil adherence. Recombinant IL-1 beta was also tested and found to induce adherence of neutrophils to human mucosal microvascular endothelial cells. However, no adhesive effect was observed with the nasal secretions of nasal allergy. An enzyme-linked immunosorbent assay detected considerable amounts of IL-1 beta in the chronic sinusitis retention fluids, while the amounts of IL-1 alpha and TNF-alpha were very low. The increased adhesion of the neutrophils by the retention fluids of chronic sinusitis was also neutralized by the incubation with anti-IL-1 beta antibody in a dose dependent manner. These findings suggest that IL-1 beta in the paranasal secretion of chronic sinusitis induces the adherence of neutrophils to vascular endothelium and subsequent infiltration of neutrophils in the paranasal sinuses, thus contributing to the persistence of chronic sinusitis.     

Respiratory symptoms and cigarette smoking in 3,197 pulmonologist-based asthmatic patients with a highly prevalent use of inhaled corticosteroid.

The relation between smoking and risk of asthma has been well-examined; however little attention has been paid to the correlation between smoking and asthma symptoms. The aims of this study were to examine respiratory symptoms in asthmatics with a highly prevalent use of inhaled corticosteroid (ICS) and to assess the effects of smoking and its cessation. A cross-sectional study of pulmonologist-based 3197 asthmatics (men 45.2%, ages 20-97) was performed using a questionnaire about smoking habits, the incidence and frequency of symptoms (sputum, cough and wheezing, night symptoms, and shortness of breath), physical activity interference, and medication. Although 81.4% of the patients used ICS according to the international guideline, 14.9% had activity interference, and daily symptoms remained in 43.3%. At the time of the questionnaire, 21.6% were current and 25.1% were ex-smokers. In multiple logistic regression analysis, the factors of significance (p < 0.0001) were (1) smoking; for all four symptoms, (2) age and duration of asthma; for shortness of breath. Current smokers were at a risk of sputum (age-adjusted odds ratio 2.32 [95% confidence interval 1.73-3.11]; 2.09 [1.57-2.79]), of cough and wheezing (2.38 [1.81-3.14]; 1.78 [1.35-2.36]), of night symptoms (1.95 [1.41-2.60]; 1.47 [1.09-1.98]), and of shortness of breath (1.70 [1.26-2.28]; 1.30 [0.97-1.75]) in men and women, respectively. These ratios in ex-smokers decreased to the level similar to nonsmokers. Although 81.4% of asthmatic patients used ICS, 43.3% complained of daily respiratory symptoms, especially sputum. It is suggested that the effects of ICS on asthma symptoms may be interfered with by smoking and therefore more emphasis should be placed on cessation of smoking.     

Inhibition of inward rectifier K+ currents by angiotensin II in rat atrial myocytes: lack of effects in cells from spontaneously hypertensive rats.

We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi-dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells.     

The trajectory of the sympathetic nerve fibers to the rat cochlea as revealed by anterograde and retrograde WGA-HRP tracing

Wheat germ agglutinin-horseradish peroxidase conjugate was injected in the unilateral superior cervical ganglion (SCG), and the projection pathways of postganglionic sympathetic nerve fibers innervating the cochlea were traced in the rat. The labeled axons advanced along the internal carotid artery (ICA), and a few advanced caudally in the major petrosal nerve (MPN) and entered the facial nerve, while the majority ran rostral to the pterygopalatine ganglion at the point where they crossed the MPN in the carotid canal. The rest of the labeled fibers remained on the surface of the ICA and advanced to the cranial cavity. Most of the labeled fibers along the facial nerve joined the cochlear nerve and finally reached the osseous spiral lamina through the spiral ganglion. Some of the labeled fibers ran along the anterior inferior cerebellar artery from the basilar artery which was previously thought to have been the only pathway. We could not find any labeled fiber on the modiolar artery from anterior inferior cerebellar artery in the cochlea. These observations are consistent with our hypothesis that the sympathetic fibers innervating the neural tissues or related structures follow nerve fibers and meninges as matrices of projection pathways rather than arteries.